The goals of these studies are to better understand the mechanism and regulation of the synthesis and degradation of the nonessential amino acid proline. The strategy primarily involves delineation of naturally occurring and laboratory induced genetic defects in proline metabolism. By characterizing these mutant cell lines we hope to learn more about both abnormal and normal proline metabolism. Recently we have shown that an important enzyme in proline biosynthesis, ornithine aminotransferase, is defective in a human disease known as gyrate atrophy of the choroid and retina. How this inborn error effects proline metabolism and urea cycle metabolism is currently under investigation.